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重组肿瘤坏死因子-α和粒细胞巨噬细胞集落刺激因子对人中性粒细胞和单核细胞趋化性及超氧化物反应的调节作用

Modulation of human neutrophil and monocyte chemotaxis and superoxide responses by recombinant TNF-alpha and GM-CSF.

作者信息

Kharazmi A, Nielsen H, Bendtzen K

机构信息

State Serum Institute, Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.

出版信息

Immunobiology. 1988 Sep;177(4-5):363-70. doi: 10.1016/S0171-2985(88)80004-4.

DOI:10.1016/S0171-2985(88)80004-4
PMID:2848761
Abstract

The effects of recombinant TNF and GM-CSF on human peripheral blood neutrophil and monocyte chemotaxis and the superoxide response were studied. TNF exhibited a slight chemotactic activity for both cell types. Preincubation of neutrophils with as little as 40 units/ml strongly inhibited the neutrophil chemotaxis towards f-Met-Leu-Phe. The inhibition of monocyte chemotaxis required higher concentrations of TNF (greater than 400 units/ml). TNF at concentrations higher than 500 units/ml enhanced the generation of superoxide anions by neutrophils stimulated with f-Met-Leu-Phe. In contrast, TNF even at 2,000 units/ml did not prime monocytes for enhanced superoxide response. GM-CSF alone did not exhibit any chemotactic activity for any of the cell types tested. Preincubation of cells with GM-CSF inhibited chemotaxis of neutrophils but not of monocytes. GM-CSF was as potent as TNF in enhancing the generation of superoxide response by neutrophils. However, GM-CSF did not have any effect on monocyte superoxide response. The priming ability of TNF and GM-CSF on neutrophils was heat-sensitive. We conclude that TNF and GM-CSF play a more pronounced regulatory role on neutrophils than on monocytes. Inhibition of neutrophil chemotaxis followed by enhancement of the superoxide response by TNF and GM-CSF may provide an attractive mechanism by which these cytokines assist in fighting invading microorganisms.

摘要

研究了重组肿瘤坏死因子(TNF)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)对人外周血中性粒细胞和单核细胞趋化性及超氧化物反应的影响。TNF对两种细胞类型均表现出轻微的趋化活性。用低至40单位/毫升的TNF预孵育中性粒细胞,可强烈抑制其对f-甲硫氨酰-亮氨酰-苯丙氨酸(f-Met-Leu-Phe)的趋化性。抑制单核细胞趋化性需要更高浓度的TNF(大于400单位/毫升)。浓度高于500单位/毫升的TNF可增强f-Met-Leu-Phe刺激的中性粒细胞超氧阴离子的生成。相反,即使浓度为2000单位/毫升的TNF也不能使单核细胞对超氧化物反应增强。单独的GM-CSF对所测试的任何细胞类型均未表现出任何趋化活性。用GM-CSF预孵育细胞可抑制中性粒细胞的趋化性,但不能抑制单核细胞的趋化性。GM-CSF在增强中性粒细胞超氧化物反应生成方面与TNF一样有效。然而,GM-CSF对单核细胞超氧化物反应没有任何影响。TNF和GM-CSF对中性粒细胞的启动能力对热敏感。我们得出结论,TNF和GM-CSF对中性粒细胞的调节作用比对单核细胞更为明显。TNF和GM-CSF先抑制中性粒细胞趋化性,随后增强其超氧化物反应,这可能提供了一种有吸引力的机制,通过该机制这些细胞因子协助对抗入侵的微生物。

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